Delivery of Active Agents

• US 20090111749A1
• Filed: 10/24/2008
• Published: 04/30/2009
• Est. Priority Date: 10/24/2007
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Costello, Donald, Richardson, Peter, Leone-Bay, Andrea, Baughman, Robert A.
• Granted Patent: US 8,372,804 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin

Abstract

A method of introducing a physiologically-active agent into the circulatory system of a mammal is disclosed herein. The method utilizes a rapid drug delivery system which prevents deactivation or degradation of the active agent being administered to a patient in need of treatment. In particular, the drug delivery system is designed for pulmonary drug delivery such as by inhalation, for delivery of the active agents such as proteins and peptides to the pulmonary circulation in a therapeutically effective manner avoiding degradation of the active agents in peripheral and vascular tissue before reaching the target site.

Claims

1. A method of providing an active agent to a patient in need thereof comprising:

selecting an active agent subject to degradation in said patient wherein the effectiveness of said active agent is reduced by said degradation;

associating said active agent with a diketopiperazine to produce a pharmaceutical composition suitable for pulmonary inhalation; and

providing said pharmaceutical composition to said patient.

2. The method of claim 1 wherein said degradation occurs in venous blood circulation, in a peripheral tissue, in the gastrointestinal system or in the liver.

3. The method of claim 1, wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine;

wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl;

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1, wherein the pharmaceutical composition is an inhalable dry powder formulation.

5. The method of claim 4, wherein said inhalable dry powder formulation further comprises a pharmaceutically acceptable carrier or excipient.

6. The method of claim 4, wherein the inhalable dry powder formulation is provided to said patient by pulmonary inhalation using a dry powder inhalation system.

7. The method of claim 1, wherein the active agent is a protein, a peptide, or an analog thereof.

8. The method of claim 1, wherein the active agent is an endocrine hormone or an analog thereof.

9. The method of claim 8, wherein the endocrine hormone is a hormone associated with diabetes, hyperglycemia and/or obesity.

10. The method of claim 9, wherein the diabetes is type 2 diabetes mellitus.

11. A method of treating disease comprising:

selecting a patient being treated with or a patient with a condition treatable by a labile active agent;

providing a composition comprising said labile active agent in association with a diketopiperazine; and

administering said composition to said patient via pulmonary inhalation;

thereby treating said disease or condition.

12. The method of claim 11, wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine;

wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl;

or a pharmaceutically acceptable salt thereof.

13. The method of claim 11, wherein said composition is an inhalable dry powder formulation.

14. The method of claim 13, wherein said inhalable dry powder formulation further comprises a pharmaceutically acceptable carrier or excipient.

15. The method of claim 11, wherein the active agent is a peptide or a protein or an analog thereof.

16. The method of claim 11, wherein the active agent is an endocrine hormone or an analog thereof.

17. The method of claim 16, wherein the endocrine hormone is a hormone associated with diabetes, hyperglycemia and/or obesity.

18. The method of claim 17, wherein the diabetes is type 2 diabetes mellitus.

19. The method of claim 11, wherein the step of administering said composition to said patient comprises pulmonary administration of said composition using a dry powder inhaler comprising a cartridge.